CD4 and HIV-1 infection: The main differences between HIV-1 and HIV-2 regarding their interactions with CD4+ T cells and MDDCs include: (i) a potentially lower level of HIV-2 replication in primary activated CD4+ T cells; (ii) a distinct molecular mechanism to target non-activated CD4+ T cells (HIV-2 necessitates Vpx, whereas HIV-1 infection occurs without the need of a Vpx-like activity); (iii) a low efficiency of HIV-2 infection in MDDCs despite the presence of Vpx.